Metabolic Reprogramming in COVID-19

Abstract

Plenty of research has revealed virus induced alternations in metabolic pathways, which is known as metabolic reprogramming. Studies focusing on COVID-19 have uncovered significant changes in metabolism, resulting in the perspective that COVID-19 is a metabolic disease. Reprogramming of amino acid, glucose, cholesterol and fatty acid is distinctive characteristic of COVID-19 infection. These metabolic changes in COVID-19 have a critical role not only in producing energy and virus constituent elements, but also in regulating immune response, offering new insights into COVID-19 pathophysiology. Remarkably, metabolic reprogramming provides great opportunities for developing novel biomarkers and therapeutic agents for COVID-19 infection. Such novel agents are expected to be effective adjuvant therapies. In this review, we integrate present studies about major metabolic reprogramming in COVID-19, as well as the possibility of targeting reprogrammed metabolism to combat virus infection.

Keywords: COVID-19; arginine; cholesterol; fatty acids; glucose; metabolic changes; tryptophan.

Figure 1

Altered tryptophan and arginine metabolism in COVID-19 patients. In COVID-19 infection, tryptophan metabolism is upregulated through kynurenine pathway. Mucus production is stimulated via IDO-Kyn-AhR pathway, resulting in hypoxia of COVID-19. Arginine depletion and increased glutamine metabolism is also discovered in COVID-19 patients. IFN, interferon; IDO, indoleamine-2,3-dioxygenase; AhR, aryl hydrocarbon receptor.

Figure 2

Schematic view of how SARS-CoV-2 enhances glycolysis and subsequent pathological change. SARS-CoV-2 induces glycolysis in a ROS/HIF-1α dependent way. Increased glycolysis fosters replication of SARS-CoV-2 and cytokine storm, giving rise to T cell impairment and lung epithelial cell death. ROS, reactive oxygen species; HIF, hypoxia-inducible factor.

Figure 3

The role of cholesterol in regulating the entry of SARS-CoV-2. HDL-scavenger receptor B type 1 (SR-B1) facilitates SARS-CoV-2 entry in an ACE2-dependent manner. Accumulation of lipid droplets is a marked characteristic of SARS-CoV-2 infected cells. 25HC depletes accessible cholesterol from plasma membrane by stimulating the ER-localized ACAT, thus suppressing membrane fusion of SARS-CoV-2. HDL, high-density lipoprotein; SR-B1, scavenger receptor B type 1; ACE2, angiotensin-converting enzyme 2; 25HC, 25-hydroxycholesterol; ER, endoplasmic reticulum; ACAT, acyl-CoA:cholesterol acyltransferase.

Figure 4

Metabolic reprogramming and corresponding therapeutic approaches in COVID-19. In COVID-19, tryptophan metabolism, glycolysis and fatty acid metabolism are upregulated, while cholesterol and arginine are decreased. Therapeutic agents targeting the reprogrammed metabolism in COVID-19 are shown in the figure. TCA, trichloroacetic acid; ROS, reactive oxygen species; HIF, hypoxia-inducible factor; FAS, fatty acid synthesis; HMG-CoV, 3-hydroxy-3-methylglutaryl-coenzyme A; IDO, indoleamine-2,3-dioxygenase.